Hayden Feddock, Francisco Yandun, Srđan Aćimović
et al.
Large-scale orchard production requires timely and precise disease monitoring, yet routine manual scouting is labor-intensive and financially impractical at the scale of modern operations. As a result, disease outbreaks are often detected late and tracked at coarse spatial resolutions, typically at the orchard-block level. We present an autonomous mobile active perception system for targeted disease detection and mapping in dormant apple trees, demonstrated on one of the most devastating diseases affecting apple today -- fire blight. The system integrates flash-illuminated stereo RGB sensing, real-time depth estimation, instance-level segmentation, and confidence-aware semantic 3D mapping to achieve precise localization of disease symptoms. Semantic predictions are fused into the volumetric occupancy map representation enabling the tracking of both occupancy and per-voxel semantic confidence, building actionable spatial maps for growers. To actively refine observations within complex canopies, we evaluate three viewpoint planning strategies within a unified perception-action loop: a deterministic geometric baseline, a volumetric next-best-view planner that maximizes unknown-space reduction, and a semantic next-best-view planner that prioritizes low-confidence symptomatic regions. Experiments on a fabricated lab tree and five simulated symptomatic trees demonstrate reliable symptom localization and mapping as a precursor to a field evaluation. In simulation, the semantic planner achieves the highest F1 score (0.6106) after 30 viewpoints, while the volumetric planner achieves the highest ROI coverage (85.82\%). In the lab setting, the semantic planner attains the highest final F1 (0.9058), with both next-best-view planners substantially improving coverage over the baseline.
Ahmed E. Abdulgalil, Noha H. Elnagdy, Nehal M. Ramadan
et al.
Abstract Introduction Mycophenolate Mofetil (MMF) has become one of the cornerstone treatments of lupus nephritis (LN). It is converted into mycophenolic acid (MPA), an active metabolite, that displays high inter- and intra-individual pharmacokinetic variability. However, the routine monitoring of MPA trough level is still debatable. Objectives The present study aims to evaluate the relationship between MPA trough levels and both clinical outcomes and drug-related adverse effects during the maintenance phase of LN in Egyptian patients. Methods We included thirty-five adults and twenty-nine children with biopsy-proven class III and IV LN, who had been maintained on steroid and MMF as maintenance therapy for more than six months. Clinical and laboratory markers of lupus activity as well as MMF adverse events were reported. MPA trough levels were measured by High-Performance Liquid Chromatography (HPLC). Results There was a significant association between low MPA trough levels and both flares and SLEDAI scores in the adult group (P = 0.027 and 0.019, respectively). Moreover, high MPA trough levels were associated with higher risk of gastritis in the same age group (P = 0.007). There was no significant association with any of the parameters studied in the pediatric group. Gastritis was the most frequent side effect in both age groups. Conclusion MPA trough levels correlated with disease activity and gastritis in adult LN patients, and this may help to optimize MMF dosage in these patients. However, MPA concentration-effect relationships were not observed in pediatric patients.
Pediatrics, Diseases of the musculoskeletal system
Dalia G Mahran, Ahmed A. Khalifa, Abdelhafeez Hamdi Abdelhafeez
et al.
Abstract Objectives The study's objectives were to assess the sarcopenia prevalence in hip fracture patients admitted to a North African (Egyptian) level one specialized trauma unit and to evaluate factors associated with sarcopenia. Methods This was an analytic, cross-sectional study where patients who were admitted with low-energy hip fractures and managed surgically were included. Assessment was performed using the SARC-F questionnaire, InBody device assessments (skeletal muscle mass (SMM), Fat mass, nutritional status (total water, protein, and minerals)), handgrip strength, and body mass index (BMI). Sarcopenia was diagnosed based on the revised European Working Group on Sarcopenia in Older People criteria (EWGSOP2). Results The patients' mean age was 68 ± 8.3 years; 51.9% were females. The mean SMM was 24 ± 4.5 kg, while the mean handgrip strength was 20.55 ± 7.66 kg, sum SARC-F score was normal in 115 (85.2%) patients and abnormal in 20 (14.8%). Based on the EWGSOP2 criteria, 23 (17%) patients had sarcopenia, and 112 (83%) did not. The two groups were comparable regarding age and sex (p = 0.907 and 0.623, respectively). Sarcopenic patients had significantly lower values in BMI (21.9 vs. 25.9 kg/m2, p < 0.001), SMM (14.8 vs. 23, p < 0.001), BMR (p < 0.001), Fat mass (18.8 vs. 24.3, p = 0.003), and handgrip strength (16 vs. 20 kg, p = 0.034), however the sum SARC-F score ≥ 4 points, was higher in sarcopenic group (30.4% vs. 11.6%, p = 0.046). SMM, BMR, and fat mass showed large effect sizes (≥ 5), while the handgrip strength showed a medium effect size (0.3). There was a significant negative correlation between patients' age and handgrip strength (r = -0.394, p < 0.001), and a significant positive correlation between BMI and the SMM (r = 0.210, p = 0.014). Univariate logistic regression analysis revealed that the patient’s BMI, fat mass, total water, protein, minerals, and the sum of SARC-F were significantly associated with sarcopenia development. However, on multivariate logistic regression analysis, two factors kept a significant association: the protein levels as a marker of nutritional reserve (OR = 0.044, 95%CI = 0.008 to 0.235, P < 0.001) and the sum SARC-F ≥ 4 points as a proxy for functional decline (OR = 6.365, 95%CI = 1.272 to 31.854, P = 0.024). Conclusion The sarcopenia prevalence in our hip fracture patients was 17%, where BMI, fat mass, and nutritional status had a significant negative association; on the other hand, the sum of SARC-F (≥ 4 points) had a significant positive association. However, after multivariate analysis, only protein levels and the sum of SARC-F remained significantly associated with sarcopenia.
Orthopedic surgery, Diseases of the musculoskeletal system
Abstract Background Posterior hemivertebra resection (HVR) with fusion is a widely accepted technique for congenital early-onset scoliosis (CEOS). However, the optimal fusion length remains debated. This study compares the long-term clinical and radiographic outcomes, as well as complication profiles, of two-level fusion (Fused_2) versus multi-level fusion (Fused_GT2) following single-stage posterior HVR in CEOS patients with minimum 10-year follow-up. Methods We retrospectively reviewed 42 CEOS patients who underwent single-stage posterior HVR and pedicle screw fixation before age 10 between August 2003 and March 2014. Patients were stratified into Fused_2 (n = 15) and Fused_GT2 (n = 27) groups based on the number of fused segments. Demographics, surgical parameters (operative time, estimated blood loss), radiographic measures (main and compensatory curves, apical vertebral translation, coronal and sagittal balance, segmental kyphosis, thoracic kyphosis, lumbar lordosis), and complications (crankshaft phenomenon, proximal junctional kyphosis, neurological events, pulmonary complications, adding-on, and reoperation) were assessed preoperatively, immediately postoperatively, and at final follow-up. Comparisons utilized Welch’s t-test and Fisher’s exact test, with p < 0.05 as significant. Results Mean follow-up was 11.02 ± 1.24 years. Fused_2 demonstrated significantly shorter operative time (150.3 ± 38.6 vs. 199.5 ± 52.2 min; p = 0.001) and lower blood loss (262.7 ± 193.2 vs. 322.2 ± 188.5 mL; p = 0.342). Preoperative main curve (28.7°±11.5 vs. 42.6°±15.1; p = 0.002) and compensatory caudal curve (9.3°±6.5 vs. 14.3°±8.6; p = 0.040), segmental kyphosis (10.4°±11.0 vs. 22.5°±15.1; p = 0.005), and thoracic kyphosis (15.9°±11.4 vs. 26.9°±16.1; p = 0.014) were significantly smaller in Fused_2, reflecting selection criteria based on deformity severity. Both groups achieved comparable immediate and final correction rates for main and compensatory curves, and similar improvements in apical translation, coronal/sagittal balance, and lumbar lordosis. Crankshaft phenomenon occurred in 35.7% overall (46.7% vs. 29.6%; p = 0.325), PJK in 14.3% (6.7% vs. 18.5%; p = 0.395), and reoperation rate 16.7% (13.3% vs. 18.5%; p > 0.999), with no significant intergroup differences. Conclusions Both two- and multi-level fusion after posterior HVR achieve sustained deformity correction and acceptable complication profiles in CEOS over ≥ 10 years. Fusion length selection should consider HV location, deformity severity, and kyphotic component to balance operative morbidity with long-term stability. Larger studies are warranted to further clarify the relationship between curve magnitude, kyphotic components, and the extent of fusion through regression analysis. Trial registration This study is a retrospective analysis and was not prospectively registered.
Orthopedic surgery, Diseases of the musculoskeletal system
George D. Kalliolias, Efthimia K. Basdra, Athanasios G. Papavassiliou
Abstract CAR-T cells (CAR-Ts) are genetically engineered T lymphocytes to express a receptor construct bearing an extracellular recognition domain that guides the killing specificity, a transmembrane domain, and an intracellular domain that elicits effector signaling. Upon encountering the target cell, CAR-Ts accomplish their cytolytic effector function directly via engagement of pro-apoptotic pathways and exocytosis of perforin and granzymes, or indirectly via secretion of cytokines that activate NK cells. Autologous CAR-Ts, bearing an extracellular recognition domain specific for the B-cell surface markers CD19 or BCMA, were initially approved for the treatment of late-stage hematologic malignancies. The last five years, mounting evidence from small studies in humans, employing autologous CAR-Ts targeting CD19 to selectively eliminate CD19 + cell subsets from the pool of the B-cell lineage, have revealed acceptable safety profile and encouraging efficacy in treatment-resistant systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myositis. Herein, we focus on a series of groundbreaking reports published within 2025 that enlighten the arising transformational potential and the emerging challenges of the CAR-based therapies regarding the management of life-threatening endotypes of autoimmune diseases.
As global living standards improve and medical technology advances, many infectious diseases have been effectively controlled. However, certain diseases, such as the recent COVID-19 pandemic, continue to pose significant threats to public health. This paper explores the evolution of infectious disease modeling, from early ordinary differential equation-based models like the SIR framework to more complex reaction-diffusion models that incorporate both temporal and spatial dynamics. The study highlights the importance of numerical methods, such as the Runge-Kutta method, implicit-explicit time-discretization techniques, and finite difference methods, in solving these models. By analyzing the development and application of these methods, this research underscores their critical role in predicting disease spread, informing public health strategies, and mitigating the impact of future pandemics.
Michael Schirmer, Lukas Kampik, Johannes D. Pallua
Recent developments in digital health technologies are overwhelming, and their use in routine work is still difficult to anticipate. This narrative review summarizes the concept of consecutive cohorts in the literature, together with local research experiences in consecutive rheumatic outpatients. Digital health techniques have to reflect the clinicians’ needs, support real-life care of patients, and allow for the specific assessment of quality parameters fulfilling the Donabedian aspect of qualified health care, using quality indicators to improve health care and research. Rapidly growing observational cohorts will perform best to provide follow-up data as the basis for further development of healthcare approaches for rheumatic patients. The challenges of a selection bias, patients with limited disease expression, and chances of early detection of patients with rare diseases are addressed. For research purposes, sequential analyses with growing cohort size, comparative cross-sectional studies with sequential hypothesis testing and other prognostic, diagnostic, and therapeutic aspects of patient management can be performed. With the support of new technologies, young clinicians can easily approach such clinical topics, and learn about clinical data analyses. The use of quality standards as proposed in international recommendations for diagnostic issues and classification criteria, management recommendations, monitoring, and training issues can be supported by digital technologies. In conclusion, collaborative projects allow detailed clinical analyses of large cohorts, but local initiatives can prepare these co-operations, provide first local logistics and research experiences, and teach clinicians how to perform clinical research. Digital health technologies will strongly support these local initiatives.
Objective: Although type II collagen could have marked potential for developing cartilage tissue engineering (CTE) scaffolds, its erratic supply and viscous nature have limited these studies, and there are no studies on the use of marine-derived type II collagen fibrils for CTE scaffold materials. In this study, we aimed to generate a fibril-based, thin-layered scaffold from marine-derived type II collagen and investigate its chondrogenic potential. Methods: Time-lapse observations revealed the cell adhesion process. The Cell Counting Kit-8 (CCK-8) assay, light microscopy, and scanning electron microscopy were performed to detect proliferation and filopodium morphology. Alcian blue staining was used to show the deposition of extracellular secretions, and qRT-PCR was performed to reveal the expression levels of chondrogenesis-related genes. Results: The cell adhesion speed was similar in both fibril-coated and control molecule-coated groups, but the cellular morphology, proliferation, and chondrogenesis activity differed. On fibrils, more elongated finer filopodia showed inter-cell communications, whereas the slower proliferation suggested an altered cell cycle. Extracellular secretions occurred before day 14 and continued until day 28 on fibrils, and on fibrils, the expression of the chondrogenesis-related genes Sox9 (p < 0.001), Col10a1 (p < 0.001), Acan (p < 0.001), and Col2a1 (p = 0.0049) was significantly upregulated on day 21. Conclusion: Marine-derived type II collagen was, for the first time, fabricated into a fibril state. It showed rapid cellular affinity and induced chondrogenesis with extracellular secretions. We presented a new model for studying chondrogenesis in vitro and a potential alternative material for cell-laden CTE research.
Le-Ying Ni,1– 3,* Cheng-Biao Ding,1,2,4,* Ji-Min Deng,5 Zheng-Wei Wu,4,6,7 Yun Zhou1,2 1Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China; 3Department of Rehabilitation Medicine, Maanshan People’s Hospital, Maanshan, Anhui, People’s Republic of China; 4School of Nuclear Science and Technology, University of Science and Technology of China, Hefei, People’s Republic of China; 5Anhui institute for Food and Drug Control, Hefei, People’s Republic of China; 6CAS Key Laboratory of Geospace Environment, University of Science and Technology of China, Hefei, People’s Republic of China; 7Institute of Advanced Technology, University of Science and Technology of China, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zheng-Wei Wu, University of Science and Technology of China, Hefei, 230026, People’s Republic of China, Tel/Fax +86-551-63606045, Email wuzw@ustc.edu.cn Yun Zhou, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China, Tel +86-0551-65997010, Email zhouyunanhui@sina.comBackground: Rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) have become the core effector cells for the progression of rheumatoid arthritis due to their “tumor-like cell” characteristics, such as being able to break free from growth restrictions caused by contact inhibition, promoting angiogenesis, invading surrounding tissues, and leading to uncontrolled synovial growth. In recent years, cold air plasma (CAP) has been widely recognized for its clear anticancer effect. Inspired by this, this study investigated the inhibitory effect of CAP on the tumor-like biological behavior of RA-FLS through in vitro experiments.Methods: Treatment of RA-FLS with CAP at different time doses (0s, 30s, 60s, 120s). 5-ethynyl-2’-deoxyuridine (EdU) proliferation assay was used to determine the cell viability. Analysis of cell migration and invasion was performed by wound-healing assay, transwell assay and immunofluorescent staining for f-actin, respectively. Flow cytometry technique was used for analysis of cell cycle and determination of reactive oxygen species (ROS). Hoechst staining was used for analysis of cell apoptosis. Protein expression was analyzed by Western blot analysis.Results: Molecular and cellular level mechanisms have revealed that CAP blocks RA-FLS in the G2/M phase by increasing intracellular reactive oxygen species (ROS), leading to increased apoptosis and significantly reduced migration and invasion ability of RA-FLS.Conclusion: Overall, CAP has significant anti proliferative, migratory, and invasive effects on RA-FLS. This study reveals a new targeted treatment strategy for RA.Keywords: cold air plasma, rheumatoid arthritis fibroblast-like synovial cells, proliferation, apoptosis, migration
Abstract Background To evaluate the effectiveness of instrument-assisted soft tissue mobilization (IASTM) on range of motion (ROM). Methods We performed a literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to December 23, 2023. Randomized controlled trials that compared treatment groups receiving IASTM to controls or IASTM plus another treatment(s) to other treatment(s) among healthy individuals with or without ROM deficits, or patients with musculoskeletal disorders were included. The Cochrane risk of bias tool was used to assess the risk of bias. Results Nine trials including 450 participants were included in the quantitative analysis. The IASTM was effective in improving ROM in degree in healthy individuals with ROM deficits and patients with musculoskeletal disorders (n=4) (MD = 4.94, 95% CI: 3.29 to 6.60), and in healthy individuals without ROM deficits (n=4) (MD = 2.32, 95% CI: 1.30 to 3.34), but failed to improve ROM in centimeter in healthy individuals with ROM deficits (n=1) (MD = 0.39, 95% CI: -1.34 to 2.11, p=0.66, I2 = 88%). Conclusions IASTM can improve ROM in degree in healthy individuals with or without ROM deficits, or in patients with musculoskeletal disorders (with very low to low certainty). Trial registration The PROSPERO registration ID is CRD42023425200.
Neurodegenerative diseases are associated with the assembly of specific proteins into oligomers and fibrillar aggregates. At the brain scale, these protein assemblies can diffuse through the brain and seed other regions, creating an autocatalytic protein progression. The growth and transport of these assemblies depend on various mechanisms that can be targeted therapeutically. Here, we use spatially-extended nucleation-aggregation-fragmentation models for the dynamics of prion-like neurodegenerative protein-spreading in the brain to study the effect of different drugs on whole-brain Alzheimer's disease progression.
Infectious disease modeling is used to forecast epidemics and assess the effectiveness of intervention strategies. Although the core assumption of mass-action models of homogeneously mixed population is often implausible, they are nevertheless routinely used in studying epidemics and provide useful insights. Network models can account for the heterogeneous mixing of populations, which is especially important for studying sexually transmitted diseases. Despite the abundance of research on mass-action and network models, the relationship between them is not well understood. Here, we attempt to bridge the gap by first identifying a spreading rule that results in an exact match between disease spreading on a fully connected network and the classic mass-action models. We then propose a method for mapping epidemic spread on arbitrary networks to a form similar to that of mass-action models. We also provide a theoretical justification for the procedure. Finally, we show the advantages of the proposed methods using synthetic data that is based on an empirical network. These findings help us understand when mass-action models and network models are expected to provide similar results and identify reasons when they do not.
Gerold Schmitt-Ulms, Xinzhu Wang, Joel Watts
et al.
Decades after their initial observation in prion-infected brain tissues, the identities of virus-like dense particles, varicose tubules, and oval bodies containing parallel bands and fibrils have remained elusive. Our recent work revealed that a phenotype of dilation of the endoplasmic reticulum (ER), most notable for the perinuclear space (PNS), contributes to spongiform degeneration. To assess the significance of this phenotype for the etiology of prion diseases, we explored whether it can be functionally linked to other neuropathological hallmarks observed in these diseases, as this would indicate it to be a central event. Having surveyed the neuropathological record and other distant literature niches, we propose a model in which pathogenic forms of the prion protein poison raft domains, including essential Na+, K+-ATPases (NKAs) embedded within them, thereby triggering an ER-centered cellular rescue program coordinated by the unfolded protein response (UPR). The execution of this program stalls general protein synthesis, causing the deterioration of synaptic spines. As the disease progresses, cells selectively increase sterol biosynthesis, along with ribosome and ER biogenesis. These adaptive rescue attempts cause morphological changes to the ER which manifest as ER dilation or ER hypertrophy in a manner that is influenced by Ca2+ influx into the cell. The nuclear-to-cytoplasmic transport of mRNAs and tRNAs interrupts in late stage disease, thereby depriving ribosomes of supplies and inducing them to aggregate into a paracrystalline form. In support of this model, we share previously reported data, whose features are consistent with the interpretation that 1) the phenotype of ER dilation is observed in major prion diseases, 2) varicose tubules and oval bodies represent ER hypertrophy, and 3) virus-like dense particles are paracrystalline aggregates of inactive ribosomes.
Shree. Dolax Ray, Mst. Khadija Tul Kubra Natasha, Md. Azizul Hakim
et al.
Carrot is a famous nutritional vegetable and developed all over the world. Different diseases of Carrot has become a massive issue in the carrot production circle which leads to a tremendous effect on the economic growth in the agricultural sector. An automatic carrot disease detection system can help to identify malicious carrots and can provide a guide to cure carrot disease in an earlier stage, resulting in a less economical loss in the carrot production system. The proposed research study has developed a web application Carrot Cure based on Convolutional Neural Network (CNN), which can identify a defective carrot and provide a proper curative solution. Images of carrots affected by cavity spot and leaf bright as well as healthy images were collected. Further, this research work has employed Convolutional Neural Network to include birth neural purposes and a Fully Convolutional Neural Network model (FCNN) for infection order. Different avenues regarding different convolutional models with colorful layers are explored and the proposed Convolutional model has achieved the perfection of 99.8%, which will be useful for the drovers to distinguish carrot illness and boost their advantage.
Yeganeh Madadi, Mohammad Delsoz, Priscilla A. Lao
et al.
Objective: To evaluate the efficiency of large language models (LLMs) such as ChatGPT to assist in diagnosing neuro-ophthalmic diseases based on detailed case descriptions. Methods: We selected 22 different case reports of neuro-ophthalmic diseases from a publicly available online database. These cases included a wide range of chronic and acute diseases that are commonly seen by neuro-ophthalmic sub-specialists. We inserted the text from each case as a new prompt into both ChatGPT v3.5 and ChatGPT Plus v4.0 and asked for the most probable diagnosis. We then presented the exact information to two neuro-ophthalmologists and recorded their diagnoses followed by comparison to responses from both versions of ChatGPT. Results: ChatGPT v3.5, ChatGPT Plus v4.0, and the two neuro-ophthalmologists were correct in 13 (59%), 18 (82%), 19 (86%), and 19 (86%) out of 22 cases, respectively. The agreement between the various diagnostic sources were as follows: ChatGPT v3.5 and ChatGPT Plus v4.0, 13 (59%); ChatGPT v3.5 and the first neuro-ophthalmologist, 12 (55%); ChatGPT v3.5 and the second neuro-ophthalmologist, 12 (55%); ChatGPT Plus v4.0 and the first neuro-ophthalmologist, 17 (77%); ChatGPT Plus v4.0 and the second neuro-ophthalmologist, 16 (73%); and first and second neuro-ophthalmologists 17 (17%). Conclusions: The accuracy of ChatGPT v3.5 and ChatGPT Plus v4.0 in diagnosing patients with neuro-ophthalmic diseases was 59% and 82%, respectively. With further development, ChatGPT Plus v4.0 may have potential to be used in clinical care settings to assist clinicians in providing quick, accurate diagnoses of patients in neuro-ophthalmology. The applicability of using LLMs like ChatGPT in clinical settings that lack access to subspeciality trained neuro-ophthalmologists deserves further research.
Neridronate or ((6-amino-1-hydroxy-1-phosphonohexyl) phosphonic acid) is an amino-bisphosphonate (BP) synthetized in Italy in 1986. Bisphosphonates are molecules with a P-C-P bond in their structure that allows strong and selectively binding to hydroxyapatite (HAP) as well as osteoclasts inhibition through different mechanisms of action. Neridronate was initially used to treat Paget disease of the bone, demonstrating effectiveness in reducing bone turnover markers as well as pain. The interesting molecular properties of neridronate foster its wide use in several other conditions, such as osteogenesis imperfecta, and osteoporosis. Thanks to the unique safety and efficacy profile, neridronate has been used in secondary osteoporosis due to genetic, rheumatic, and oncological diseases, including in pediatric patients. In the last decade, this drug has also been studied in chronic musculoskeletal pain conditions, such as algodystrophy, demonstrating effectiveness in improving extraskeletal outcomes. This review highlights historical and clinical insights about the use of neridronate for metabolic bone disorders and musculoskeletal pain conditions.